Dendritic cells in autoimmune disease

Dendritic cells (DC) are a group of sparsely distributed "professional" antigen presenting cells. Most DC are relatively short-lived cells that must be continually renewed by precursors from bone marrow. Their characteristic form led to their recognition as a distinct cell type by Steinman and Cohn in 1973. Subsequent work revealed their key function in the adaptive immune system: the collection, processing, and presentation of peptide fragments of antigens to T cells on major histocompatibility complex (MHC) molecules. The exceptional ability of DC to process and present antigens and so to activate even naïve T cells has endowed them with the title of "professional" antigen presenting cells. In steady state DC play a role in lymphocyte specificity selection and the maintenance of peripheral tolerance. However, DC serve as the sentinels of the immune system and are rapidly activated, via innate response mechanisms, by pathogens or host factors that signal danger or stress. Activated DC produce cytokines and other factors that contribute to inflammatory responses. Upon activation those sentinel DC in peripheral tissues migrate to lymph nodes to allow contact with T cells. The activated DC presenting antigen-MHC complexes then activate antigen-specific T cells to initiate immune responses. The nature of the subsequent response is in part determined by factors produced by the DC. DC thus link the innate and the adaptive immune systems.DC constitute 1% or less of the cells in various tissues of the body. Different types of DC occur in different anatomical locations and even within one location. These DC subsets differ in surface phenotype and in specialized aspects of DC function. This diversity of DC subsets is key to obtaining the appropriate immunological response to different pathogen challenges. However, together with the low number of DC it presents a daunting obstacle to determining the role of DC in human disease. This chapter aims to address the functional aspects of different types of DC relevant to autoimmunity, with specific examples of functions contributing to autoimmune disease etiology